tbuckley/cabot-search huggingface dataset:
Abstract 6156: High-fat diet-induced gut dysbiosis promotes prostate cancer growth through mast cells and histamine 1 receptor
Authors: Kazutoshi Fujita, Makoto Matsushita, Daisuke Motooka, Takuaki Hase, Eri Banno, Marco De Velasco, Taigo Kato, Atsunari Kawashima, Motohide Uemura, Shota Nakamura, Kazutake Tsujikawa, Eiichi Morii, Kazuhiro Yoshimura, Hirotsugu Uemura
Journal: Cancer Research (2022)

Abstract Introduction and Objective High-fat diet (HFD) induce prostate inflammation and promote cancer growth. However, the mechanism of this inflammation has not been entirely clear. We provide the evidence of new histamine-mediated mechanism and the crucial role of the gut microbiota on HFD-induced prostate cancer (PCa) growth. Methods We compared between HFD-fed and control diet (CD)-fed prostate-specific Pten KO mice at 22 weeks of age as PCa models. HFD-fed mice were given histamine receptor antagonist. Tumor growth was evaluated by prostate weight and Ki67 staining. Gut microbiota compositions were analyzed by 16S rRNA gene sequencing. Histamine signaling in PCa was assessed at gene and protein level. Results HFD significantly increased prostate weight (0.25 vs. 0.46g, P = 0.01) and Ki67-positive cancer cell ratio (0.15 vs. 0.36, P = 0.01). cDNA microarray of PCa showed that expression of Hdc encoding histidine decarboxylase (HDC), which is responsible for histamine production, was upregulated in HFD-fed mice (Fold change = 2.71). The elevated expression of Hdc was also confirmed by quantitative PCR (P &amp;lt; 0.01). Infiltrating mast cells highly produced HDC protein, and mast cell counts around cancer foci were significantly increased in HFD-fed mice. Fexofenadine (Fexo), an H1 blocker, inhibited HFD-induced PCa growth, while ranitidine, an H2 blocker, had no inhibitory effect. Fexo reduced MDSC counts and suppressed IL6-STAT3 signaling in PCa of HFD-fed mice. In vitro, both histamine and Fexo did not affect the proliferation of DU145. HFD altered the composition of gut microbiota, and Shannon index suggesting diversity of gut microbiota was reduced in HFD-fed mice. Serum lipopolysaccharide (LPS) levels were elevated in 11-week-old HFD-fed mice, and LPS injection resulted in upregulation of Hdc in PCa. Conclusions We found that HFD caused gut microbiota dysbiosis and elevated systemic LPS level, which could promote inflammatory PCa progression through mast cells and histamine H1 receptor signaling. These results suggest the existence of “Gut-Prostate Axis.” Citation Format: Kazutoshi Fujita, Makoto Matsushita, Daisuke Motooka, Takuaki Hase, Eri Banno, Marco De Velasco, Taigo Kato, Atsunari Kawashima, Motohide Uemura, Shota Nakamura, Kazutake Tsujikawa, Eiichi Morii, Kazuhiro Yoshimura, Hirotsugu Uemura. High-fat diet-induced gut dysbiosis promotes prostate cancer growth through mast cells and histamine 1 receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6156.
Abstract 707: Mahanine, a carbazole alkaloid attenuates lung cancer progression
Authors: Raghuram Kandimalla, Farrukh Aqil, Disha N. Moholkar, Suman K. Samanta, Ramesh C. Gupta
Journal: Cancer Research (2022)

Abstract Lung cancer continues to be a major cause of cancer mortality. Emerging evidence suggests that cancer likely involves multiple mutations. Therefore, compounds targeting multiple signal transduction pathways would be ideal for the prevention and treatment of cancer. Mahanine, a carbazole alkaloid isolated from an Indian folklore medicinal plant Murraya koenigii (known as Curry Patta), widely consumed in traditional dishes, have been shown to possess anticancer activities and confound many oncogenic signaling events in breast, colon, and prostate cancers. In the current study, we determined the anticancer potential of mahanine against drug-sensitive and drug-resistant lung cancer cells and postulate the possible mechanism of action. Mahanine was isolated from the dried leaves of Murraya koenigii by hydro alcoholic extraction and fractionation with ethyl acetate, followed by preparative UPLC to isolate pure (&amp;gt;95%) compound and its identity was confirmed by LC-MS/MS and NMR spectroscopy. Antiproliferative activity of mahanine was determined against drug- sensitive (A549 and H1299) and taxol-resistant (A549-TR) human lung cancer cells. Mahanine showed a dose- and time-dependent inhibition of both drug-sensitive and drug-resistant lung cancer cell growth. Interestingly, the IC50 values of mahanine were essentially the same for drug sensitive (A549) (12.5 µM) and drug- resistant (12.5 µM) lung cancer cells; the IC50 value was somewhat lower (10 µM) against highly metastatic H1299 lung cancer cells. Mahanine attenuated the colony formation and reduced the wound healing of lung cancer cells. Mechanistically, mahanine dose dependently impeded the oncogenic markers such as KRAS, MET, AKT, mTOR and cMYC. Together, mahanine demonstrate ability to inhibit both drug- sensitive and drug-resistant lung cancer cells and modulate distinct oncogenic molecular targets providing potential to be developed for the treatment of drug-resistant and metastatic NSCLC (Supported from Duggan Endowment funds). Keywords: Mahanine, Lung cancer, Oncogenes, Plant therapeutics. Citation Format: Raghuram Kandimalla, Farrukh Aqil, Disha N. Moholkar, Suman K. Samanta, Ramesh C. Gupta. Mahanine, a carbazole alkaloid attenuates lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 707.
Abstract 2803: A renewable IHC control tool CytoSections࣪ for defining MAGEA3, MAGEA4, and MAGEA9 antibody specificity
Authors: Eden B. Zewdu, Rachel M. Gonzalez, Yan Ma, Derek Ling, Xiaomin Hu, Qi Ren, Ranran Zhang, Li-Hui Lei, Krishnan Allampallam, Dezhong Yin, Xuan Liu, Wei Fu
Journal: Cancer Research (2022)

Abstract Melanoma-associated antigen gene A (MAGEA) family proteins are expressed in a variety of tumors with each MAGEA protein having unique roles in cancer pathogenesis. The MAGEA members lack of expression in normal tissue and their role in cancer make them well suited for targeted cancer immunotherapy. Thus, knowing which MAGEA protein expression exists in a tumor is important. However, the MAGEA family shares sequence similarity that makes it difficult to find antibodies that are specific to just one family member. It is also challenging to source tissue generally with HIPAA regulation and even more so to get tissue representation of all 12 MAGEA family members. Here we present CytoSections as an alternative to patient control tissues. CytoSections are formalin fixed, paraffin embedded (FFPE) section of over-expression cell pellets. These cells were transfected with expression plasmids coding for genes of individual MAGES family. In this study, CytoSections are used to screen antibodies to all 12-member MAGEA family of proteins. The MAGEA family members were initially shown positive by targeted protein expression in western and immunohistochemistry using DDK tag antibody. Then multiple MAGEA3, MAGEA4, MAGEA9 antibodies were assessed by IHC to determine their specificity to their intended target. Using MAGEA family as a pilot project, we show that CytoSections is a verified, reproducible, and renewable alternative to human control tissues and serves as an ideal tool for antibody specificity assessment. Citation Format: Eden B. Zewdu, Rachel M. Gonzalez, Yan Ma, Derek Ling, Xiaomin Hu, Qi Ren, Ranran Zhang, Li-Hui Lei, Krishnan Allampallam, Dezhong Yin, Xuan Liu, Wei Fu. A renewable IHC control tool CytoSections࣪ for defining MAGEA3, MAGEA4, and MAGEA9 antibody specificity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2803.
Abstract 5671: Thermotherapy interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of ovarian cancer to oxaliplatin
Authors: Fangrong Shen
Journal: Cancer Research (2022)

Abstract At present, hyperthermia combined with chemotherapy has become a clinical treatment means Despite some research reports investigating the effects of heat elevation on inducing the DNA damage response and interfering with various DNA repair pathways, but the underlying coalition mechanisms of combined with PARP inhibitorss are not yet completely elucidated. In this study, We use a variety of OC cell lines treat by thermo-chemotherapy and then the proliferation, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Here, We found that in heat sensitive cell line A2780cells treat by thermo-chemotherapy combined wint PARPi, could induces Ppromote OC cells apoptosis and inhibit proliferation, aggravate DNA damage and arrests OC in the cell cycle S phase, buthowever, in heat resistance cell line SKOV3 cells there exhibited an Constant tendency. Western blot analysis shows hyperthermia down-regulated the levels of PARP1 and XRCC1.In addition, hyperthermia combined with chemotherapy could increase the expressions of ATM and NBS1 in the double-stranded DNA damage pathway. Meanwhile, The expression of DNA damage-related proteins increased after PARP1 inhibitors eliminated single-strand repair. Based on these results, we conclude hyperthermia confers sensitization of ovarian cancer to oxaliplatin via interference with XRCC1/PARP1-mediated base excision repair be consumed and Promotes DNA double strand breakage, thereby inhibiting OC development. Citation Format: Fangrong Shen. Thermotherapy interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of ovarian cancer to oxaliplatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5671.
Abstract 3253: Probing the effects of retinoblastoma binding protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells
Authors: Pontsho Moela, Harshini Mehta, Melvin Ambele
Journal: Cancer Research (2022)

Abstract RBBP6 is considered a potential cancer biomarker due to its association with cell proliferation and the fact that it is overexpressed at cervical cancer sites where there is marked apoptosis and elevated p53. More information is emerging regarding the role of RBBP6 in cancer treatment, specifically its potential to sensitize cancer cells to radiation and certain chemotherapeutic agents via BCL-2 gene regulation. Cisplatin is an FDA-approved chemotherapeutic agent that still presents with acquired resistance in certain cervical cancer cases through p53 repression and BCL-2 upregulation, which is why there is ongoing research in trying to understand the molecular mechanisms involved in the response of cervical cancer cells to this drug. The present study therefore aims to investigate the possible relationship between cisplatin and RBBP6 expression in cervical cancer cells. RBBP6 was silenced in Hela, CaSki and Vero cells using the RNAi technology, followed by measurement of wild-type p53 and BCL-2 at mRNA level using qPCR. Cells co-treated with cisplatin and siRBBP6 were therefore analyzed for apoptosis induction and real time growth monitoring using flow cytometry and the xCELLigence system, respectively. Cancer cells in the co-treatment group showed a reduction in apoptosis compared to cisplatin-only group and real time growth monitoring revealed a reduced growth rate in RBBP6-knockdown cells treated with cisplatin. Although wild-type p53 remained unchanged in the co-treatment group of cancer cells, BCL-2 was completely repressed, suggesting that RBBP6 is necessary for the responsiveness of cervical cancer cells to via BCL-2 downregulation. Findings from this study suggest that RBBP6 expression promotes sensitivity of HeLa cells to cisplatin through BCL-2 downregulation. Knockdown of RBBP6 limits apoptosis induction and delays cell growth inhibition in response to cisplatin. The knowledge obtained here has the potential to help improve cisplatin efficacy through personalized administration based on the expression profile of RBBP6 among individual patients. Citation Format: Pontsho Moela, Harshini Mehta, Melvin Ambele. Probing the effects of retinoblastoma binding protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3253.
Abstract 6015: Comprehensive evaluation of three-dimensional (3D) culture systems as compound screening platforms with primary cancer cell lines
Authors: Chao Zhang, Qinghua Wu, Lei Jin, Deyin Chen, Xuzhen Tang, Hui Qi, Wenjie Gao, Qunsheng Ji
Journal: Cancer Research (2022)

Abstract There are a number of challenges associated with personalized medicines. For example, many models revolve around the question of whether or not the in vitro models capture the relevant in vivo pathobiology and drug response information that may impact a patient's response to a therapy. Most in vitro oncology drug screening techniques are based on two-dimensional (2D) cell culture, which, to date, has failed to accurately imitate the physiological microenvironments due to the inherent limitations, such as the lack of interactions between intracellular and extracellular environments, or modifications in three-dimensional cell morphology, polarity, and division. These disadvantages prompted the development of models which would better simulate the microenvironment of tumor cells. Three-dimensional (3D) culture systems are becoming increasingly popular due to their ability to mimic natural cell characteristics and tissue-like structures compared with traditional 2D monolayer cell culture. Currently, multicellular spheroid and organoid cell culture are two popular 3D culture methods to evaluate drug activity. Spheroid cell culture utilizes ultra-low attachment plate to allow cells grow in spheroid format. Organoid cell culture is accomplished by growing cells in extracellular matrix scaffolds (such as Matrigel). In this study, we attempted to compare different drug screening platforms, including patient-derived xenograft (PDX) and two 3D cell cultures (spheroid and organoid). Compound sensitivity, genomics, pathology and expression of clinical marker were profiled. The purpose of this study is to identify an optimal model as a drug testing platform and a bridge between in vitro studies and animal experiments for identifying novel therapeutic targets. Citation Format: Chao Zhang, Qinghua Wu, Lei Jin, Deyin Chen, Xuzhen Tang, Hui Qi, Wenjie Gao, Qunsheng Ji. Comprehensive evaluation of three-dimensional (3D) culture systems as compound screening platforms with primary cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6015.
Abstract 4097: Clinicopathologic descriptors of subcutaneous panniculitis-like T-cell lymphoma (SPTCL): Analysis of a pooled database of a rare entity
Authors: Philip A. Haddad, Nowell Ganey
Journal: Cancer Research (2022)

Abstract Introduction: SPTCL is a rare primary cutaneous T-cell lymphoma. SPTCL was initially described as an aggressive cutaneous T-cell lymphoma frequently associated with hemophagocytic syndrome (HPS) and requiring aggressive multiagent chemotherapy. In 2005, this entity was restricted to SPTCL with αβ phenotype, a less aggressive entity compared to its γδ counterpart, currently known as primary cutaneous γδ T-cell lymphoma. We conducted this analysis to explore the clinicopathologic characteristics of this little-known primary cutaneous T-cell entity. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 214 cases. Descriptive statistics were calculated. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 214 patients with confirmed SPTCL diagnosis were identified. The median age was 34 years with a peak incidence between ages 13 and 26. There was a female predominance with F:M ratio of 1.7. Upon presentation, 12% had lymphadenopathy, 12% had hepatosplenomegaly, and 27% had bone marrow involvement. No extra-nodal or extra-cutaneous involvement were reported. Cases expressed CD2 (8%), CD3 (85%), CD4(10%), CD5(10%), CD7 (9%), CD8 (77%), CD56 (6%), Granzyme-B (33%), and TIA-1 (34%). None of the cases expressed CD30. The most common clinical presentations were nodular skin changes (87%) followed by constitutional symptoms (57%). Fifteen and ten percent of SPTCL patients had history of immune-deregulatory disorders and immunosuppressive therapies, respectively. HPS occurred in 24% of the cases. Karyorrhexis, fat necrosis, and dermal involvement were noted in 15%, 9%, and 17%. The median duration of symptoms prior to diagnosis was 4 months. Median OS of the whole group was not reached while the mean OS was 73 months. OS was not impacted by sex, constitutional symptoms, immunocompromising factors, presence of lymphadenopathy, hepatosplenomegaly, or bone marrow involvement. OS was not impacted by histological or immunohistochemical features either. While older age and the occurrence of HPS negatively impacted OS, attaining complete remission positively impacted OS. Conclusions: This study presents a comprehensive clinicopathologic data from a pooled cohort of patients with SPTCL. It describes the clinicopathologic features of SPTCL and identifies major determinants of OS in this rare disease. Citation Format: Philip A. Haddad, Nowell Ganey. Clinicopathologic descriptors of subcutaneous panniculitis-like T-cell lymphoma (SPTCL): Analysis of a pooled database of a rare entity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4097.
Abstract 1000: E-cadherin and EGFR interactions result in hyper-proliferation via ERK signaling in breast cancer
Authors: Gabriella C. Russo, Ashleigh Crawford, David J. Clark, Julie Cui, Ryan Carney, Michelle N. Karl, Boyang Su, Batrholomew Starich, Tung-Shing Lee, Qiming Zhang, Pei-hsun Wu, Meng-Horng Lee, Hon S. Leong, Vito Rebecca, Hui Zhang, Denis Wirtz
Journal: Cancer Research (2022)

Abstract The loss of the intercellular adhesion molecule E-cadherin is a hallmark of the epithelial-mesenchymal transition (EMT), during which tumor cells transition into an invasive phenotype. Thus, E-cadherin has long been considered a tumor suppressor gene. However, recent studies have provided evidence that E-cadherin may promote metastasis rather than suppress it, suggesting oncogenic behavior. Here we provide data that E-cadherin plays an oncogenic role in breast cancer by promoting a hyper-proliferative phenotype in breast cancer cells via interaction with EGFR. This interaction results in the activation of the MEK/ERK signaling pathway, leading directly to changes in proliferation via transcription factors such as c-Fos. Pharmacological inhibition of MEK in E-cadherin positive breast cancer cells significantly decreases both tumor growth and macro-metastasis in vivo. This work provides evidence for a novel role of E-cadherin in breast tumor progression and identifies a potential new target to treat hyper-proliferative E-cadherin-positive breast tumors. Citation Format: Gabriella C. Russo, Ashleigh Crawford, David J. Clark, Julie Cui, Ryan Carney, Michelle N. Karl, Boyang Su, Batrholomew Starich, Tung-Shing Lee, Qiming Zhang, Pei-hsun Wu, Meng-Horng Lee, Hon S. Leong, Vito Rebecca, Hui Zhang, Denis Wirtz. E-cadherin and EGFR interactions result in hyper-proliferation via ERK signaling in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1000.
Abstract 1561: Lnc-NR2F1 upregulated by a ZEB1/NR2F1 axis promotes the migration and invasion of lung cancer cells via TWIST2 regulation
Authors: Eun Ju Kim, Young-Ho Ahn
Journal: Cancer Research (2022)

Abstract Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides lacking protein-coding potential, which are involved in diverse pathophysiologic conditions including cancer progression and metastasis. Metastasis is initiated by a cellular process, epithelial-to-mesenchymal transition (EMT), and many lncRNAs can be affected by and participate in the EMT process. To find out lncRNAs regulated by the EMT signals, we performed an NGS-based RNA sequencing in murine lung cancer cells, and finally selected lnc-NR2F1 that is upregulated by ZEB1, an EMT-inducing transcription factor. lnc-NR2F1 expression levels showed a positive correlation with ZEB1 mRNA levels and EMT scores in 13 mouse lung cancer cells or in lung adenocarcinoma data from TCGA. The migration and invasion of lung cancer cells were decreased after lnc-NR2F1 knockdown and increased after lnc-NR2F1 overexpression. lnc-NR2F1 was transcriptionally up-regulated by NR2F1, a transcription factor transcribed from the antisense strand. Interestingly, NR2F1 was transcriptionally induced by ZEB1, and promoted the migration and invasion of lung cancer cells. Through the analysis of public ChIRP-seq data, we found that lnc-NR2F1 can modulate the expression of TWIST2, and add-back of TWIST2 restored the migration and invasion of lung cancer cells suppressed by lnc-NR2F1 knockdown. In conclusion, lnc-NR2F1 is induced by a ZEB1-NR2F1 axis and stimulates the migration and invasion of lung cancer cells via transcriptional regulation of TWIST2. Citation Format: Eun Ju Kim, Young-Ho Ahn. Lnc-NR2F1 upregulated by a ZEB1/NR2F1 axis promotes the migration and invasion of lung cancer cells via TWIST2 regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1561.